| First Author | Han CR | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 18080 |
| PubMed ID | 29273766 | Mgi Jnum | J:287345 |
| Mgi Id | MGI:6407636 | Doi | 10.1038/s41598-017-18409-4 |
| Citation | Han CR, et al. (2017) NCOR1 modulates erythroid disorders caused by mutations of thyroid hormone receptor alpha1. Sci Rep 7(1):18080 |
| abstractText | Thyroid hormone receptor alpha (THRA) gene mutations, via dominant negative mode, cause erythroid abnormalities in patients. Using mice expressing a dominant negative TRalpha1 mutant (TRalpha1PV; Thra1 (PV/+) mice), we showed that TRalpha1PV acted directly to suppress the expression of key erythroid genes, causing erythroid defects. The nuclear receptor corepressor 1 (NCOR1) was reported to mediate the dominant negative effects of mutated TRalpha1. However, how NCOR1 could regulate TRalpha1 mutants in erythroid defects in vivo is not known. In the present study, we crossed Thra1 (PV/+) mice with mice expressing a mutant Ncor1 allele (NCOR1DeltaID; Ncor1 (DeltaID) mice). TRalpha1PV mutant cannot bind to NCOR1DeltaID. The expression of NCOR1DeltaID ameliorated abnormalities in the peripheral blood indices, and corrected the defective differentiation potential of progenitors in the erythroid lineage. The defective terminal erythropoiesis of lineage-negative bone marrow cells of Thra1 (PV/+) mice was rescued by the expression of NCOR1DeltaID. De-repression of key erythroid genes in Thra1 (PV/+) Ncor1 (DeltaID/DeltaID) mice led to partial rescue of terminal erythroid differentiation. These results indicate that the inability of TRalpha1PV to recruit NCOR1DeltaID to form a repressor complex relieved the deleterious actions of TRalpha1 mutants in vivo. NCOR1 is a critical novel regulator underpining the pathogenesis of erythroid abnormalities caused by TRalpha1 mutants. |
